Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Peritoneal Infection (DAPTODP)

Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Patients With Peritoneal Dialysis and Peritoneal Infection

Peritoneal infection is still a frequent complication in peritoneal dialysis patients . In France, It contributes to the technique failure, responsible for about 20% of cases of transfer in hemodialysis. The risk of direct mortality is estimated at 1 to 6% according to studies. Peritoneal infection is involved in the dysfunction of the peritoneal membrane.

Based on the recommendations of the International Society for Peritoneal Dialysis, the intraperitoneal route is preferentially recommended. For many antibiotics, pharmacokinetics (intravenous and intraperitoneal) was studied and protocols for IP administration were validated.

Daptomycin, is a cyclic lipopeptide natural, active only on Gram-positive bacteria. It is presented as an alternative to vancomycin in infections resistant pathogens. The stability of daptomycin in peritoneal dialysis fluids (PDF) has been tested, and antimicrobial activity as well.

Seven patients were treated with daptomycin intraperitoneally successfully. But no study has reported pharmacokinetics of daptomycin via the IP route. We propose a pharmacokinetic study of daptomycin administered intraperitoneally in 12 patients on CAPD and with Gram-positive peritoneal infection.

Study Overview

• Status: Completed
• Conditions: Peritoneal Infection
• Intervention / Treatment: Drug: intraperitoneal daptomycin

Detailed Description

Methodology:

Prospective, open-label, non-randomized pharmacokinetic study. Daptomycin will be given IP in the CAPD fluid (200mg in 2L Nutrineal) once daily, in a 6 hours-dwell time. The process of dialysis is done four times per day : three during the day (6,6,and 4 h) and one time at night (8h). Duration of treatment depends on bacteria identified (14 or 21 days).

Analyses will be performed on data from all patients meeting the criteria for inclusion and exclusion.

For each patient, plasma, dialysate and urine kinetics will be studied.

For each parameter, mean and standard deviation are calculated.

Number of centers & patients:

One center, twelve patients.

Sample size justification:

This is an observational pharmacokinetic study of consecutive PD patients presenting to Caen University Hospital with peritoneal infection and who meet inclusion criterias over one year.

Population: CAPD patients with a Gram positive peritoneal infection

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Caen, France, 14000
    • Néphrologie CHU de Caen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients > 18 years

• Hospitalized CAPD patients with Gram positive peritoneal infection : ISPD criterias
• Presence of two clinical signs and symptoms : abdominal pain, nausea, vomiting, diarrhea, fever and cloudy dialysate
• Peritoneal dialysate WBC>100/µL with at least 50% polymorphonuclear neutrophil cells
• Demonstration of bacteria on Gram stain or culture
• on peritoneal dialysis for at least 3 months
• written consent, obtained from either the patient, one of his/her relatives, the trusted person who was designated beforehand or, if not possible, emergency enrollment.
• patient has a life expectancy greater than 6 months

Exclusion Criteria:

• Known allergy to daptomycin
• Peritoneal infection with Gram negative only
• Patient with CPK>5UNL
• patients already treated with antibiotics, antifungals within 4 weeks prior to the event
• Patient with hepatic impairment
• Patient with arguments for an extra-peritoneal site of infection
• Patient with severe intercurrent illness (eg, hematologic malignancies, patients on chemotherapy)
• Infection by daptomycin-resistant germ
• HMGCoA reductase, fibrates or ciclosporin treatment
• Pregnant or breast-feeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intraperitoneal daptomycin; 3 first patients : 200mg/day 3 following patients : 300mg/day	Drug: intraperitoneal daptomycin; intraperitoneal daptomycin administartion and study of daptomycin kinetics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Primary endpoint : Pharmacokinetics study : Evaluation of : the maximum plasma concentration,; areas under the curve; compartments clearances,; the time during which dialysate concentration is greater than 20mg /L (5xEnterococcus CMI)	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tolerance	CPK<5N	14 days

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Investigators: Principal Investigator: Thierry Lobbedez, Pr, University Hospital, Caen; Study Director: Maxence FICHEUX, Dr, University Hospital, Caen

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: September 3, 2013
• First Submitted That Met QC Criteria: November 26, 2013
• First Posted (Estimate): December 4, 2013

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; peritoneal dialysis; peritonitis; intraperitoneal; daptomycin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Peritoneal Diseases; Disease Attributes; Intraabdominal Infections; Infections; Communicable Diseases; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 2012-005699-33